Monodentate Transient Directing Group Assisted Ruthenium(II)-Catalyzed Direct ortho-C–H Imidation of Benzaldehydes for Diverse Synthesis of Quinazoline and Fused Isoindolinone

Abstract

2-Fluoro-5-(trifluoromethyl)­aniline was found to be a suitable monodentate transient directing group (MonoTDG) to enable Ru­(II)-catalyzed intermolecular direct ortho-C­(sp2)–H imidation of benzaldehydes. N-Tosyloxyphthalimide was used as an alternative azide-free amidation reagent to achieve high efficiency and good functional group tolerance. Moreover, the reaction could be enlarged to gram scale, and the amidated product could be readily converted into useful quinazoline and fused isoindolinone scaffolds by one-step derivatization.

Transient Directing Group Strategy as a Unified Method for Site Selective Direct C4–H Halogenation of Indoles

“…8 Since the breakthrough work from Yu's group, 9 a large number of TDG-assisted direct C−H functionalizations has been implemented for benzaldehydes. 10 However, heterocyclic aldehydes have been rarely focused on, and the only two examples concerned C−H arylation. 11 There is high demand to explore other reaction variants for heterocyclic aldehydes.…”

C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

“…[21] This kind of transformation was also proposed with a ruthenium catalyst by Zhou and Zhang who achieved an ortho-CÀ Himidation reaction of benzaldehydes 31 (Scheme 9.b). [22] Prod-ucts could be easily converted into nitrogenated heterocycles such as quinazoline 33 or isoindolinone 34.…”

“…For instance, Sundararaju's group developed a cobalt(III)‐catalyzed amidation reaction with aniline to form the TDG (Scheme 9.a) [21] . This kind of transformation was also proposed with a ruthenium catalyst by Zhou and Zhang who achieved an ortho ‐C−H‐imidation reaction of benzaldehydes 31 (Scheme 9.b) [22] . Products could be easily converted into nitrogenated heterocycles such as quinazoline 33 or isoindolinone 34 .…”

Iridium-Catalyzed Direct Ortho-C–H Amidation of α-Ketoesters with Sulfonyl Azides Using a Transient Directing Group Strategy

“…Based on the structure analysis, its inert reactivity was supposed to be caused by its bidentate coordination model, resulting in a stable and rigid five-membered cyclometallic complex . In light of the success of the transient directing group (TDG)-enabled C–H amidation of benzaldehydes, we hypothesized that this newly emerged TDG strategy might provide an alternative solution for α-ketoester . The in situ generated imine as a strongly coordinating directing group could not only override the weakly coordination of carbonyl but also change the original bidentate coordination model to monodentate, so as to facilitate the ortho -C–H activation progress .…”